Objective To explore the changes in serum trace elements and its correlation with biochemical indicators and development of type 2 diabetes mellitus (T2DM) in patients with T2DM. Methods A total of 89 patients with confirmed T2DM admitted in the Endocrinology Department, Xuhui District Central Hospital of Shanghai from June 2012 to June 2014 were enrolled in this study. Another 97 non-T2DM patients (having no significant differences in age, sex, body mass index, and waist-hip ratio with the T2DM group) in our hospital at the same duration were recruited as control group. Fasting blood glucose (FBG), 2-hour postprandial glucose (2hPBG), glycosylated hemoglobin A1c (HbAlc), fasting insulin (FINS), and peptide C were measured. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the serum levels of trace elements, Fe, Zn and Se. The correlation of serum trace elements with biochemical indicators and T2DM was analyzed. Results Serum levels of Fe, Zn and Se were significantly lower in T2DM group than in control group (P＜0.05), and also remarkably reduced in the T2DM patients with HbAlc ≥7.0% than in those with HbAlc ＜7.0% (P＜0.05). Pearson correlation analysis showed that there was positive correlation between Fe and Zn, Fe and Se, and Zn and Se, respectively (r＝0.668, 0. 725, 0.754, P＜0.05). Serum levels of Fe, Zn and Se were all highly correlated with HbAlc, FBG, 2hPBG, FINS and peptide C. Multivariate logistic regression analysis showed that Zn and Se were the protective factors for T2DM (β＝-1.302, -1.578; P＜0.05). Conclusion The serum levels of trace elements are generally low in T2DM patients, and the levels are closely related to the glycometabolism. So maintaining the balance of trace elements is of positive significance in the prevention or onset delay of T2DM.